A study to assess and compare the variation of tacrolimus availability within and bewteen patients when taking an immediate-relase formulation of tacrolimus and after conversion to a formulation with prolonged release.

- candidate number

5681

- NTR Number

NTR1791

- ISRCTN

ISRCTN wordt niet meer aangevraagd

- Date ISRCTN created

- date ISRCTN requested

- Date Registered NTR

30-apr-2009

- Secondary IDs

NL26976.068.09

- Public Title

A study to assess and compare the variation of tacrolimus availability within and bewteen patients when taking an immediate-relase formulation of tacrolimus and after conversion to a formulation with prolonged release.

- Scientific Title

An open-label, single centre study to assess and compare the intra- and interpatientvariability in the oral bioavailability for Immediate-Release Tacrolimus and after conversion to Modified-Release Tacrolimus in stable kidney transplant recipients.

1. Renal transplant recipients that were transplanted at least six month before entry into the study;
2. 18 years of age or older;
3. Stable renal allograft function;
4. Immunosuppression with Tacrolimus twice daily (TAC BID);
5. Part of the population is selected on base of already known CYP3A5 SNPís (carrier or homozygous for *1) to ensure inclusion of an adequate amount of patients with an increased metabolism of tacrolimus.

Evaluation and comparison of the intra- and interpatient variability for the area under the curve (AUC) of orally administered Tac BID and Tac QD.

- Secondary outcome

1. Evaluation and comparison of the intra- and interpatient variability for pharmacokinetic parameters:
A. Maximum concentration of tacrolimus (Cmax);
B. Time to reach Cmax (Tmax);
C. Tacrolimus trough levels (Cmin).
2. Correlation of limited sampling strategies (LSS) for Tac BID and Tac QD with a 24-hour AUC;
3. Correlation of pharmacokinetic profiles with CYP3A5 SNPs;
4. Evaluation of the patients perception of Quality of Life (QOL) before and after conversion to a once-daily formulation;
5. Evaluation of the patients perception of the Blood Spot method.

- Timepoints

Weekly measurement of the AUC for TAC BID and TAC QD, respectively, during a six week period (i.e. 6 AUCs). The first AUC for TAC QD will be determined two weeks after conversion.

A modified-release formulation of Tacrolimus, a potent immuno-suppressor, has been developed which has to be taken once daily (Tac QD, Advagraf‚) instead of twice daily as is the case with the immediate-release formulation (Tac BID, Prograf‚). To our knowledge no numerical data have been published comparing the intra- and interpatient variability of the bioavailability (Area under the curve: AUC) of beforementioned formulations. This study has been designed for this purpose. 40 Stable renal transplant recipients will be converted from TAC BID to TAC QD. For each formulation 6 8-point AUCs will be determined by dried blood spot sampling. Furhtermore the acquired data will be poled towards the patient's cytochrome P 450 3A5 single nucleotide polymorphisms (SNPs).